We are examining the mechanisms by which hallucinogenic drugs produce changes in associative processes (i.e., learning) as measured by rates of acquistion of classically conditioned responses in the rabbit. Using the classically conditioned, nictitating membrane response we have found that LSD at dosages of 1 to 100 nmol/kg produces a dose-dependent enhancement in the acquistion of conditioned responses to both auditory and visual stimuli. The ED50 of LSD for enchancement of acquistion was approximately 3.3 nmol/kg, i.e., 1.4 micrograms/kg as the salt form. 300 nmol/kg LSD produces a retardation of acquistion. Separate experiments indicated that these changes in rate of acquistion of the conditioned nictitating membrane response were not due to sensitization or pseudoconditioning, nor were they due to changes in base-rate responding or in the amplitude of the unconditoned response. Therefore, these results suggest that LSD uniquely affects associative processes (learning). Moreover, animals that had already acquired the conditioned nictitating membrane response to auditory and visual stimuli were not affected by subsequent injections of 30 or 300 nmol/kg LSD, indicating that these dosages of LSD do not affect the ability of the animals to detect the conditioned stimuli or to produce the nictitating membrane response. Taken together, these data also suggest that the acquisition of a learned response may be far more sensitive to the actions of LSD than is a previously learned and well established response. We are currently determining whether these effects of LSD: 1) are related to some alterations in the processing of stimuli; 2) are produced by other hallucinogens; 3) demonstrate tolerance; and 4) are mediated via serotonin or catecholamine systems of brain.